Management of older ( 50 years old) HIV-infected individuals is becoming increasingly complex as many develop multiple HIV-associated-non-AIDS-defining (HANA) comorbidities at an earlier onset. We will utilize frailty measurements and neuropsychological performance (NP) tests to determine if a combination of cognitive impairment and frailty identifies vulnerable older HIV-infected individuals (n=130). In addition, we will employ innovative brain imaging techniques [including arterial spin labeling magnetic resonance imaging (ASL-MRI) and positron emission tomography using Pittsburgh B compound (PET-PiB)] to quantitatively assess perfusion and amyloid deposition in older HIV-infected individuals. We will evaluate if frailty correlates with neuroimaging biomarkers (ASL and PET-PIB) of brain integrity in older HIV-infected patients. Finally, we will determine at three year follow-up if frail older HIV-infected individuals have greater rates of change from baseline in cognitive impairment (NP testing), amyloid deposition (PET-PiB), and perfusion (ASL-MRI) compared to pre-frail or non-frail older HIV-infected individuals. This proposal will place HIV associated changes in frailty and cognition into the mainstream of national brain aging research. We will develop biomarkers that will allow for early detection of changes in brain function at the pre-frail state. It is hoped that these biomarkers will assist in the early administration of tailoed effective interventions.